Consequence Of Chronic Renal Failure Research Articles

Phosphate restriction using a processed clay mineral reduces vascular pathologies and microalbuminuria in rats with chronic renal failure

BackgroundThe progression of chronic kidney disease (CKD) is associated with an increasing risk of cardiovascular morbidity and mortality due to elevated serum phosphate levels. Besides low phosphate diets and hemodialysis, oral phosphate binders are prescribed to treat hyperphosphatemia in CKD patients. This study reports on a processed clay mineral as a novel and efficient phosphate sorbent with comparable efficacy of a clinically approved phosphate binder.Methods5/6 nephrectomized rats, which develop chronic renal failure (CRF), received a high phosphate and calcium diet supplemented with either a processed Montmorillonite-Illite clay mineral (pClM) or lanthanum carbonate (LaC) for 12 weeks. Levels of plasma uremic toxins, glomerular filtration rates and microalbuminuria were determined and the histomorphology of blood vessels and smooth muscle cells was analyzed.Results5/6 nephrectomy induced an increase in plasma uremic toxins levels and progressive proteinuria. Treatment of CRF rats with pClM decreased observed vascular pathologies such as vascular fibrosis, especially in coronary vessels. The transition of vascular smooth muscle cells from a contractile to a secretory phenotype was delayed. Moreover, pClM administration resulted in decreased blood creatinine and urea levels, and increased glomerular filtration rates, reduced microalbuminuria and eventually the mortality rate in CRF rats.ConclusionOur study reveals pClM as a potent phosphate binding agent with beneficial impacts on pathophysiological processes in an animal model of CKD. pClM effectively attenuates the progression of vascular damage and loss of renal function which are the most severe consequences of chronic renal failure.

Hipertensión arterial en la enfermedad renal crónica

A common comorbidity of chronic renal failure (CRF) is arterial hypertension (AHT), and it is both cause and consequence of CRF. Multiple and interrelated mechanisms are involved in AHT including hydrosaline retention, stimulation of the renin-angiotensin-aldosterone system (RAAS) and hyperactivity of the sympathetic nervous system. Diagnosis requires an accurate blood pressure measurement (BP) in medical consultancy. There is increasing evidence of the advantages of ambulatory BP monitoring and 24-hours BP measurement. Low-sodium diet is the mainstay of non-pharmacological management of AHT. In patients with proteinuria RAAS blockers are the antihypertensive drugs of choice, being mandatory to assess their side effects. In general terms, 130-139/70-79mm Hg is the goal in BP treatment, however it has to be individualized according to the patient comorbidities and the presence or not of diabetes.

HP-09-005 Sex hormone profile on hemodialysis

Sexual dysfunction is one of the numerous consequences of chronic renal failure. The aim of this study is the search for the origin of these sexual disturbances, through the investigation of the hypothalamohypophysogonadic axis in kidney failure patients. We measured FSH, LH, testosterone, prolactin and TSH in male patients undergoing hemodialysis (patient group = 55 subjects) and in virile, fertile men from Gynecology department of Tahar Sfar hospital (control group = 55 subjects). The average age of patients was 48.2 ± 11.8 years and 47.89 ± 5.93 years in control group (p = 0.87). All patients were fertile and had a normal sexual activity before undergoing hemodialysis. Patients had low testosterone value (3.84 ± 1.77 ng/mL vs 5.41 ± 2.03 ng/mL; p = 0.004) compared to control group. The levels of FSH and LH were higher in patients undergoing hemodialysis (respectively8.83 ± 6.5 UI/L vs 4.31 ± 2.62 UI/L; p = 0.002 and14.62 ± 8.86 UI/L vs 6.43 ± 3.79 UI/L; p < 0.001). Even levels of prolactin were higher significantly among these patients (respectively 465.54 ± 299.66 mU/L vs 234.66 ± 131.68 mU/L; p = 0.007). However, no significant difference was noted between the 2 groups for the LH / FSH ratio (p = 0.36). Among the study, only 5 patients had serum thyroid stimulating hormone levels above the laboratory reference range (> 4.5 mIU/L) without any differences between subjects and patients group.

Growth Hormone, Insulin-Like Growth Factor-1, and the Kidney: Pathophysiological and Clinical Implications

Besides their growth-promoting properties, GH and IGF-1 regulate a broad spectrum of biological functions in several organs, including the kidney. This review focuses on the renal actions of GH and IGF-1, taking into account major advances in renal physiology and hormone biology made over the last 20 years, allowing us to move our understanding of GH/IGF-1 regulation of renal functions from a cellular to a molecular level. The main purpose of this review was to analyze how GH and IGF-1 regulate renal development, glomerular functions, and tubular handling of sodium, calcium, phosphate, and glucose. Whenever possible, the relative contributions, the nephronic topology, and the underlying molecular mechanisms of GH and IGF-1 actions were addressed. Beyond the physiological aspects of GH/IGF-1 action on the kidney, the review describes the impact of GH excess and deficiency on renal architecture and functions. It reports in particular new insights into the pathophysiological mechanism of body fluid retention and of changes in phospho-calcium metabolism in acromegaly as well as of the reciprocal changes in sodium, calcium, and phosphate homeostasis observed in GH deficiency. The second aim of this review was to analyze how the GH/IGF-1 axis contributes to major renal diseases such as diabetic nephropathy, renal failure, renal carcinoma, and polycystic renal disease. It summarizes the consequences of chronic renal failure and glucocorticoid therapy after renal transplantation on GH secretion and action and questions the interest of GH therapy in these conditions.

Un cas historique d’hyperparathyroïdie sur une insuffisance rénale chronique négligée

Hyperparathyroidism is a common consequence of chronic renal failure. Diagnosis is most often established early during monitoring of these patients, and before complications. We report the clinical case and original imaging of a patient, in whom hyperparathyroidism with skeletal and extraskeletal complications was diagnosed, following neglected chronic renal failure.

Natural Killer Cell Dysfunction in Uremia: The Role of Oxidative Stress and the Effects of Dialysis

Immune deficiency is one of the numerous consequences of chronic renal failure. We can hypothesize that an abnormal natural killer (NK) cell response is present in patients with end-stage renal disease (ESRD). To characterize the immune defect in ESRD patients, we performed a NK cell subset analysis in 66 patients with ESRD treated by hemodialysis or peritoneal dialysis. Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D(+) cells within both CD8(+) T cell (58 vs. 67%, p = 0.03) and NK cell (39 vs. 56%, p = 0.002) populations. We further studied NK cell subsets in 55 hemodialysis patients and 17 patients treated by peritoneal dialysis. As compared to healthy donors, all these patients had significantly decreased NKG2D-positive NK cells. Patients using PMMA membranes (BK-F) or Helixone-FX membranes had a smaller decrease in NKG2D-positive NK cells when compared to patients treated with Nephral membranes. The expression of MICA on the cell surface of monocytes, which is a marker of inflammation induced by cellular stress, was also lower in patients using BK-F membranes. In conclusion, these data suggest that a subpopulation of NK cells is decreased in patients with ESRD. This decrease is associated with high circulating levels of the HLA-related molecule MICA. The dialysis membrane can influence the modulation of both the phenotype of NK cells and MICA overexpression.

Erythropoietin and Cardiovascular System

SUMMARY Erythropoietin (EPO) is a glycoprotein hormone which is essential for normal erythrocyte production in bone marrow in healthy subjects. It induces erythropoiesis under hypoxic conditions. It is released from renal peritubular cells and various extrarenal tissues like liver, spleen, brain, lungs, bone marrow, reproductive organs. Interaction of EPO with its receptor (EPO-R) decreases programmed death (apoptosis) of erythroid progenitor cells and promotes their differentiation in bone marrow. Clinically, rHuEPO (recombinant human EPO) has been used since the late 1980s in patients with anaemia due to EPO deficiency as a consequence of chronic renal failure. In addition to erythroid progenitor cells, a varied group of cells including neurons, endothelial cells, vascular smooth muscle cells, and cardiac myocytes express EPO-R. It has been shown that Epo has cytoprotective properties against ischemia reperfusion damage and hypoxia in the brain, heart, kidneys, retina, liver, lungs, and intestines. It was suggested EPO. In addition to inhibition of apoptosis, EPO exhibits many other actions that serve to protect cells either directly or indirectly. EPO should therefore be regarded also as a general tissueprotective cytokine.

Study of Blood Porphyrin Spectral Profile for Diagnosis of Chronic Renal Failure

The progression to end-stage renal failure is independent of the initial pathogenic mechanism. Metabolic acidosis is a common consequence of chronic renal failure that results from inadequate ammonium excretion and decreased tubular bicarbonate reabsorption. Protoporphyrin IX (PpIX) is the immediate metabolic precursor of the heme molecule. The purpose of this study was to evaluate the levels of erythrocytes protoporphyrin IX at an animal model during progressive renal disease. A total of 36 eight-week-old male Wistar rats were divided into six groups: Normal, 4 and 8 weeks after 5/6 nephrectomy (NX). Renal function was evaluated by creatinine clearance and plasma creatinine levels. The autofluorescence of erythrocytes porphyrin of healthy and NX rats was analyzed using fluorescence spectroscopy. Emission spectra were obtained by exciting the samples at 405 nm. Significant differences between normal and NX rats autofluorescence shape occurred in the 600-700 nm spectral region. A correlation was observed between emission band intensity at 635 nm and progression of renal disease.

Insufficient therapeutic management of hypertensive patients with renal failure in France

Hypertension is both the cause and consequence of chronic renal failure (CRF). The prevalence of CRF, which itself is a cardiovascular risk factor, is not well known in France. To estimate the prevalence of renal dysfunction among hypertensive patients who were seen by general practitioners (GP); to assess the drug management of hypertension in these patients according to their renal status. A transversal observational study among patients of both genders aged 18 or more, with arterial blood pressure greater than 130/80 mmHg (i.e., over CRF-recommended blood pressure) or under antihypertensive drugs who were recruited in France by GP. Among the 2315 included patients, 1908 could be analyzed for their renal function. Of these, 70.5% had an estimated glomerular filtration rate (GFR) of 89 ml/min per 1.73 m(2) or lower. One third of these patients (31.4%) were suffering from renal failure (GFR<or=59 ml/min per 1.73 m(2)). CRF was moderate in 27.9% of patients, severe in 2.20% and terminal (GFR<15 ml/min per 1.73 m(2)) in 1.26%. At least one antihypertensive drug was taken by 1952 patients (84.3%), regardless of the patient's renal status. Hypertensive patients who are seen by GP have a high level of renal disturbances and many of them do not reach recommended blood pressure values. This highlights the importance of an early detection of renal dysfunction avoiding progression towards end-stage renal failure and an adapted antihypertensive drugs prescription, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blocker, acting as renal protectors.

Bone Densitometric Analysis in Egyptian Hemodialysis Patients

End-stage renal failure (ESRF) is the ultimate consequence of chronic renal failure, in which case dialysis is generally required. In dialysed patients, almost all patients have abnormal bone histology and their lower values of glomerular filtration rate have been associated with lower bone mineral density (BMD) at all sites. The objective of the present study was to investigate the effect of hemodialysis (HD) on body-composition (BC), specially segmental and total BMD, in Egyptian ESRF patients. Forty ESRF patients [20 male/20 female; mean age (±SD): 52.11 ± 12.97 yr] undergoing regular HD 3 times/week (duration: 6.50 ± 5.68 yr) using bicarbonate dialysis and polysulphon membrane, and other 40 age- and sex-matched healthy controls volunteered in the study. Blood samples were obtained for monitoring serum levels of calcium (Ca), inorganic phosphate (P), osteocalcin (OC), and parathormone (PTH) for all participants. BC was evaluated by dual X-ray absorptiometry. HD patients manifested lower segmental and total BMD values in comparison with age-matched healthy controls (Z-score: -0.17±1.12) due to significantly higher levels of P (4.04 ± 1.33 vs. 3.39 ± 0.51 mg/dl, p &lt; 0.001), PTH (538.17 ± 363.99 vs. 48.86 ± 19.64 ng/L, p &lt; 0.0001), and OC (50.39 ± 34.91 vs. 16.32 ± 5.37 mg/L, p &lt; 0.0001). Pelvis, lumbar spine, and total BMD (g/cm2) for HD patients were significantly correlated with HD duration (yr) (R = 0.94, 80, and 92, respectively, p &lt; 0.0001). Thus, BC analysis is of utmost importance for efficiently providing tailored individual mineral supplementation to HD patients.

Intestinal phosphate absorption in a model of chronic renal failure

Hyperphosphatemia is an important consequence of chronic renal failure (CRF). Lowering of the plasma phosphate concentration is believed to be critical in the management of patients with CRF, especially those on dialysis. Reports of the effect of CRF on the intestinal handling of phosphate in vitro have been conflicting; but what happens in vivo has not been studied. What effect a reduction in the dietary phosphate intake has on intestinal phosphate absorption in CRF in vivo is unclear. In this study, we have used the in situ intestine loop technique to determine intestinal phosphate absorption in the 5/6-nephrectomy rat model of CRF under conditions of normal and restricted dietary phosphate intake. In this model of renal disease, we found that there is no significant change in the phosphate absorption in either the duodenum or jejunum regardless of the dietary phosphate intake. There was also no change in the expression of the messenger RNA of the major intestinal phosphate carrier the sodium-dependent-IIb transporter. Furthermore, we found no change in the intestinal villus length or in the location of phosphate uptake along the villus. Our results indicate that in CRF, unlike the kidney, there is no reduction in phosphate transport across the small intestine. This makes intestinal phosphate absorption a potential target in the prevention and treatment of hyperphosphatemia.

Correction of Anemia in Uremic Rats by Intramuscular Injection of Lentivirus Carrying an Erythropoietin Gene

Background: Anemia is an inevitable consequence of chronic renal failure. Gene therapy using lentiviral vector (LV) would be an effective tool to treat anemia associated with renal failure. Methods: A LV carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. Polymerase chain reaction assays were done to validate the presence of the LV in the experimental rats. Results: After a single intramuscular injection of LV at a dose of 55 µg p24 Gag antigen (∼5 × 10⁷ transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 ± 4.2%, p < 0.01, n = 8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 ± 3.3%, p < 0.01, n = 3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 ± 4.1% (n = 8) at 3 weeks and 33.1 ± 3.7% (n = 4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p < 0.01) to 156.3 ± 3.0 mU/ml compared to the control rats (63.9 ± 1.7 mU/ml). Polymerase chain reaction analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney, were negative. Conclusions: This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tool to deliver secretable proteins at therapeutic levels in various animal disease models.

Body Growth after Combined Liver-Kidney Transplantation in Children with Primary Hyperoxaluria Type 1

Children with primary hyperoxaluria type 1 (PH1) often develop severe growth failure, which is related to metabolic and endocrine consequences of chronic renal failure, and/or oxalate deposition in bone and cartilage. Combined liver and kidney transplantation (LKT) corrects the underlying metabolic defect and restores renal function in these children. We therefore analyzed longitudinal growth of 24 children with PH1 who underwent LKT at nine European centers. Mean age at LKT was 8.9 years, and mean duration of follow-up was 5.7 years. After LKT mean standardized height tended to increase from -1.79 SD to -1.47 SD until last observation. Mean adult height amounted to 167 cm and 158 cm in boys and girls, respectively. At last observation, seven out of 24 patients were stunted. Within the whole study population, the degree of catch-up growth after LKT was positively associated with degree of stunting at the time of LKT and negatively associated with prednisolone dosage explaining together 39% of the overall variability. Combined LKT does not induce true catch-up growth in the majority of children with PH1. Due to the preexisting growth retardation at the time of LKT, one third of patients end up with a reduced final height.

675. Correction of Anemia in Uremic Rats by Intramuscular Injection of Lentivirus Carrying an Erythropoietin Gene

Anemia is an inevitable consequence of chronic renal failure. A lentiviral vector (LV) carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. After a single intramuscular injection of LV at a dose of 55 mg p24 Gag antigen (|[sim]|5 |[times]| 107 transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 |[plusmn]| 4.2%, p<0.01, n=8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 |[plusmn]| 3.3%, p<0.01, n=3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 |[plusmn]| 4.1% (n=8) at 3 weeks and 33.1 |[plusmn]| 3.7% (n=4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p<0.01) to 156.3 |[plusmn]| 3.0 g/dL compared to the control rats (63.9 |[plusmn]| 1.7 g/dL). Polymerase chain reaction (PCR) analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney were negative. This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tools to deliver secretable proteins at therapeutic levels in various animal disease models.

Biochemical Consequences of Chronic Renal Failure. By M. R. Wills, M.D., M.R.C. Path., London. 9 × 6 in. Pp 218, with 9 illustrations. 1971. Aylesbury: Harvey Miler &amp; Metcalf Ltd. £3

Journal Article Biochemical Consequences of Chronic Renal Failure. By M. R. Wills, M.D., M.R.C. Path., London. 9 × 6 in. Pp 218, with 9 illustrations. 1971. Aylesbury: Harvey Miler & Metcalf Ltd. £3 Get access Biochemical Consequences of Chronic Renal Failure. By M RWills, M.D., M.R.C. Path., London. 9 × 6 in. Pp 218, with 9 illustrations. 1971. Aylesbury: Harvey Miler & Metcalf Ltd. £3. British Journal of Surgery, Volume 59, Issue 3, March 1972, Page 248, https://doi.org/10.1002/bjs.1800590338 Published: 07 December 2005

Oro-dental health in children with chronic renal failure and after renal transplantation: a clinical review

As a consequence of chronic renal failure (CRF) and its treatment, a number of oro-dental changes occur that persist after the end-stage is reached. An early effect is enamel hypoplasia due to a defect of enamel development and mineralisation. This is usually reparable to a high aesthetic standard using dental composite filling material. Children with CRF have significantly less dental caries than healthy children due to the inhibitory effect of increased salivary urea levels. Grafted patients frequently develop gingival enlargement as a result of immunosuppression with cyclosporine A, which is further exacerbated by the additional use of antihypertensive calcium-blocking agents. Surgical reduction of gingival hyperplasia is effective and is required in approximately one third of adolescents. A very high standard of home care should be encouraged for all children with CRF in the form of thorough mechanical tooth cleaning and plaque inhibition through the use of an antibacterial mouthwash. In transplanted children presenting an increased risk of infection, antibiotic prophylaxis may be indicated for dental treatment procedures. The drug dosage should be adapted to the reduced renal function. Pediatric nephrologists should be aware that dental surgeons can make a considerable contribution to the general health and well-being of children with CRF. Thus, only oro-dental problems that are mainly encountered and treated by dental surgeons are reviewed.

Calcium citrate ameliorates the progression of chronic renal injury

Metabolic acidosis is a consequence of chronic renal failure and it may produce bone demineralization, muscle proteolysis, and progression of chronic renal failure. The aim of this study was to evaluate the effects of correction of metabolic acidosis with calcium citrate in an experimental model of renal mass ablation. Wistar rats were subjected to 5/6 nephrectomy and were randomly assigned to one of 4 groups: nontreated (NFX); treated with calcium citrate (1.45 g/100 g feed) (NFX-CIT); treated with captopril (500 mg/L water) (NFX-CAP); or treated with both (NFX-CAP-CIT) during 1, 10, or 20 weeks. Body weight, systolic blood pressure, proteinuria, arterial bicarbonate concentration, urine citrate excretion, plasma calcium, and inulin clearance were measured. Histologic glomerular and tubulointerstitial damage scores were measured at 1, 10, and 20 weeks, and glomerular and tubular proliferating cell nuclear antigen (PCNA)-positive cells, alpha-smooth muscle actin, and desmin staining were studied by immunohistochemistry at 1 and 10 weeks. The treated groups showed significantly less glomerular and tubulointerstitial cellular proliferation in the first week (P < 0.05), less glomerular cell transdifferentiation and higher plasma bicarbonate at 10 weeks (P < 0.05), as well as diminished histologic glomerular and tubulointerstitial damage scores at 20 weeks (P < 0.05). Inulin clearances were higher (P < 0.05), and urine protein excretion rates were lower (P < 0.05) than in the NFX non-treated group, but arterial blood pressure was not significantly different in the NFX-CIT group. Calcium citrate slows the progression of chronic renal injury in the 5/6 NFX model. It improves metabolic acidosis and diminishes cell proliferation and transdifferentiation without changes in systolic blood pressure.

GI manifestations of chronic renal failure

Abstract The gastrointestinal (GI) manifestations of chronic renal failure (CRF) can be viewed in 3 categories: (1) GI manifestations that are the consequence of CRF, (2) GI manifestations associated with the treatment of CRF including dialysis and renal transplantation with associated chronic immunosuppression, and (3) GI manifestations of diseases associated with both GI dysfunction as well as CRF. CRF rarely is associated with distinct manifestations of GI dysfunction. The major manifestation is an increased risk for GI bleeding, associated with vascular lesions of the GI tract. The GI consequences of treatment of renal failure including dialysis, transplantation, and immunosuppression may be diverse and protean. Dialysis is associated with an increased risk for viral hepatitis. Immunosuppression is associated with opportunistic infections. In addition, drugs associated with posttransplant immunosuppression predispose to gastritis, peptic ulcer disease, and mucosal injury, as well as drug-induced pancreatits and hepatitis. Finally, numerous multisystem diseases may be etiologic for both GI and hepatic dysfunction as well as CRF. These disorders include diabetes, arteriosclerotic vascular disease, collagen vascular diseases, and autoimmune diseases. Copyright 2002, Elsevier Science (USA). All rights reserved.

Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management

Hyperphosphatemia is a predictable consequence of chronic renal failure and is present in most patients on dialysis. Traditionally, the risk associated with elevated serum phosphorus has focused on its impact on renal osteodystrophy. A growing body of evidence, however, suggests that abnormalities in serum phosphorus, calcium-phosphorus product (CaxP), and parathyroid hormone (PTH) levels are resulting in vascular and visceral calcification, thereby contributing to the substantially increased risk of cardiovascular death in this population. In this analysis, we review in detail the literature that describes these associations. We show that the current treatment paradigm for serum phosphorus and secondary hyperparathyroidism is ineffective for a large segment of dialysis patients. Currently, 60% of hemodialysis patients have phosphorus greater than 5.5 mg/dL, and 40% have CaxP greater than 60 mg2/dL2. It is our belief that prevention of uremic calcification, cardiac death, and vascular disease should assume primary importance when evaluating the risks associated with elevated levels of phosphorus, CaxP, and PTH. We recommend that target levels should become 9.2 to 9.6 mg/dL for calcium, 2.5 to 5.5 mg/dL for phosphorus, less than 55 mg2/dL2 for CaxP product, and 100 to 200 pg/mL for intact PTH.

Intermediate term results of total lymphoid irradiation for the treatment of non-specific graft dysfunction after heart transplantation.

A proportion of heart transplant recipients develop poor graft function in the absence of cellular infiltrate in endomyocardial biopsies or transplant associated coronary artery disease. The condition has a poor prognosis and its aetiology is poorly understood. We report encouraging intermediate term results with total lymphoid irradiation (TLI) in the management of this condition. Eleven adult cardiac transplant recipients who developed severe allograft dysfunction (NYHA class-4) at a median period of 4 months after orthotopic heart transplantation were successfully treated with TLI. Endomyocardial biopsies and coronary angiography were normal in each patient and biventricular failure developed in spite of immunosuppression with Cyclosporin-A, Azathioprine, oral Prednisolone, Cyclophosphamide and intravenous Methylprednisolone therapy. Total lymphoid irradiation was given with standard Mantle and inverted Y-fields over ten treatments to achieve a cumulative dose of 8 Gy. Each patient had a significant improvement in clinical response and in ventricular performance within 2 months of commencing TLI. Nine patients are currently well (four NHYA class-1, five NHYA class-2) at 4-48 (median 26) months following TLI. Two patients died; one from bacterial septicaemia and one as a consequence of chronic renal failure. Three patients developed opportunistic infection which was successfully treated with appropriate antimicrobial agents. An Ebstein-Barr virus associated lymphoproliferative disorder occurred in one patient and was successfully treated by reduction in immunosuppression and high dose Acyclovir. Two patients developed transient bone marrow suppression. The intermediate term results of TLI in the management of poor graft function in cardiac transplant recipients with normal endomyocardial biopsies and coronary angiography are encouraging. Although complications of opportunistic infection, bone marrow suppression and lymphoproliferative disorder occurred, treatment was successful in each case.